m-Trifluoromethyl-diphenyl diselenide attenuates pentylenetetrazole-induced seizures in mice by inhibiting GABA uptake in cerebral cortex slices

Pharmacol Rep. Nov-Dec 2009;61(6):1127-33. doi: 10.1016/s1734-1140(09)70175-6.

Abstract

The present study investigated the anticonvulsive effect of the disubstituted diaryl diselenides diphenyl diselenide (PhSe)(2), m-trifluoromethyl-diphenyl diselenide (m-CF(3)-C(6)H(4)Se)(2), p-chloro-diphenyl diselenide (p-Cl-C(6)H(4)Se)(2) and p-methoxyl-diphenyl diselenide (p-CH(3)O-C(6)H(4)Se)(2) on a chemical model of seizure induced by pentylenetetrazole (PTZ) in mice. (PhSe)(2), (p-Cl-C(6)H(4)Se)(2) and (p-CH(3)O-C(6)H(4)Se)(2) did not abolish seizures induced by PTZ in mice. (m-CF(3)-C(6)H(4)Se)(2) at the dose of 100 mg/kg significantly prolonged the latency of the onset of the first convulsive episode and reduced the number of animals that presented seizures. To investigate the possible mechanisms involved in the anticonvulsant effect of (m-CF(3)-C(6)H(4)Se)(2), mice were submitted to different associations (all drugs in a sub-effective dose); aminooxyacetic acid hemihydrochloride (AOAA, a gamma-aminobutyric acid (GABA)-T inhibitor), diazepam (a GABA(A) receptor agonist) or DL-2,4-diamino-n-butyric acid hydrochloride (DABA, an inhibitor of GABA uptake) were pre-administered together with (m-CF(3)-C(6)H(4)Se)(2). (m-CF(3)-C(6)H(4)Se)(2) + DABA abolished seizures induced by PTZ in mice. (m-CF(3)-C(6)H(4)Se)(2) administered alone or with PTZ decreased the levels of GABA uptake in cerebral cortex slices. The present study demonstrates that (m-CF(3)-C(6)H(4)Se)(2) exerts anticonvulsant action by decreasing the levels of GABA uptake.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / chemistry
  • Anticonvulsants / pharmacology*
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / pharmacology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Disease Models, Animal
  • Female
  • Mice
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology
  • Organosilicon Compounds / pharmacology*
  • Pentylenetetrazole
  • Seizures / drug therapy*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Anticonvulsants
  • Benzene Derivatives
  • Organoselenium Compounds
  • Organosilicon Compounds
  • m-trifluoromethyl-diphenyl diselenide
  • diphenyldiselenide
  • gamma-Aminobutyric Acid
  • Pentylenetetrazole